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Biomedical subjects

K Kumano

Publications and source records attributed to K Kumano.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nitric oxide formation in the dog sphincter of Oddi from nitric oxide donors as measured with in vivo micro-dialysis.

BACKGROUND: Nitric oxide (NO) is known to play an important role in neurally mediated relaxation of the sphincter of Oddi. AIM: We investigated whether NO donors, such as nitroglycerin or zwitterionic polyamine/NO, applied into the common bile duct or intravenously, may induce the relaxation of the sphincter of Oddi by producing NO in the anaesthetized dog. METHODS: NO production in the sphincter of Oddi was measured by detecting NO oxidation products (NO2- and NO3-) using micro-dialysis methods. RESULTS: Zwitterionic polyamine/NO and nitroglycerin applied into the common bile duct induced a marked increase in NO2- but not NO3-, in the sphincter of Oddi. Intravenous infusion of zwitterionic polyamine/NO and nitroglycerin induced little or no increase in NO2- formation. Nitroglycerin infused into either the common bile duct or intravenously administered produced relaxation of the sphincter of Oddi, but zwitterionic polyamine/NO had no effect on the sphincter of Oddi in spite of the increase in NO2- levels. CONCLUSIONS: Locally or systemically applied NO donors induce relaxation of the sphincter of Oddi by producing NO, although their mode of action differs in different analogues.

Animals↗
PubMed2000

Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2.

Delta1, Jagged1, and Jagged2, commonly designated Delta/Serrate/LAG-2 (DSL) proteins, are known to be ligands for Notch1. However, it has been less understood whether they are ligands for Notch receptors other than Notch1. Meanwhile, ligand-induced cleavage and nuclear translocation of the Notch protein are considered to be fundamental for Notch signaling, yet direct observation of the behavior of the Notch molecule after ligand binding, including cleavage and nuclear translocation, has been lacking. In this report, we investigated these issues for Notch2. All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells, although characteristics of Jagged2 for binding to Notch2 apparently differed from that of Delta1 and Jagged1. After binding, the three DSL proteins induced cleavage of the membrane-spanning subunit of Notch2 (Notch2(TM)), which occurred within 15 min. In a simultaneous time course, the cleaved fragment of Notch2(TM) was translocated into the nucleus. Interestingly, the cleaved Notch2 fragment was hyperphosphorylated also in a time-dependent manner. Finally, binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. Together, these data indicate that all of these DSL proteins function as ligands for Notch2. Moreover, the findings of rapid cleavage, nuclear translocation, and phosphorylation of Notch2 after ligand binding facilitate the understanding of the Notch signaling.

Animals↗
PubMed2000

Systemic T helper 2 cell activation is not sufficient for antigen-induced eosinophil recruitment into the airways.

BACKGROUND: Airway eosinophilic inflammation is a characteristic feature of asthma. We have previously shown that antigen-induced eosinophil recruitment into the airways of sensitized BALB/c mice is mediated by CD4+ T cells and IL-5. However, the basis for the eosinophil recruitment into the airway are still largely unknown. METHODS: To determine the regulatory mechanisms that control the magnitude of antigen-induced eosinophilic inflammation in the airways, we analyzed antigen-induced eosinophil and T cell infiltration into the trachea in several strains of mice, including BALB/c (H-2(d)), BALB/b (H-2(b)), C57BL/6 (H-2(b)), C57BL/10 (H-2(b)), and B10.D2 (H-2(d)) mice. In addition, cytokine production from antigen-stimulated splenocytes and the titer of antigen-specific IgE antibody in serum were assessed. RESULTS: Antigen-induced eosinophil recruitment into the trachea in BALB/c mice was more than 20 times as abundant as that in C57BL/6 mice, the latter of which was also mediated by CD4+ T cells. In contrast, systemic Th2 responses, which were evaluated by the titers of antigen-specific IgE antibody in serum and antigen-induced IL-4 and IL-5 production from splenocytes, were similarly observed in BALB/c mice and C57BL/6 mice. In addition, the antigen-induced eosinophil recruitment into the trachea was high in BALB/b mice, like BALB/c mice, but low in B10.D2 mice. CONCLUSIONS: Systemic Th2 responses are not sufficient for causing antigen-induced eosinophil recruitment into the airways and an undefined determinant(s) that exists in the BALB background mice rather than the H-2 haplotype is vital for the regulation of antigen-induced eosinophil recruitment into the airways.

Animals↗
PubMed2000

Sigmoid sinus thrombosis after mild closed head injury in an infant: diagnosis by magnetic resonance imaging in the acute phase--case report.

Intracranial sinus thrombosis following a mild closed head injury without a skull fracture or intracranial hematoma is extremely rare. A 23-month-old girl presented with vomiting and gait ataxia 1 day after occipital trauma. Computed tomography revealed a slightly increased density area in the region of the left sigmoid sinus. T1-weighted magnetic resonance (MR) imaging demonstrated an isointense area in the left sigmoid sinus and T2-weighted imaging showed a hyperintense area reflecting the characteristics of oxyhemoglobin. MR angiography and cerebral angiography indicated occlusion of the left sigmoid sinus. After 4 days of conservative treatment, her symptoms subsided completely. Follow-up MR angiography and cerebral angiography showed recanalization of the sigmoid sinus. The MR images and MR angiograms were useful for both early diagnosis and follow-up. Treatment should reflect the severity of individual cases, and early diagnosis will help achieve a good outcome.

Acute Disease↗
PubMed1999

Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods.

The Delta/Serrate/LAG-2 (DSL) domain containing proteins are considered to be ligands for Notch receptors. However, the physical interaction between DSL proteins and Notch receptors is poorly understood. In this study, we cloned a cDNA for mouse Jagged1 (mJagged1). To identify the receptor interacting with mJagged1 and to gain insight into its binding characteristics, we established two experimental systems using fusion proteins comprising various extracellular parts of mJagged1, a "cell" binding assay and a "solid-phase" binding assay. mJagged1 physically bound to mouse Notch2 (mNotch2) on the cell surface and to a purified extracellular portion of mNotch2, respectively, in a Ca(2+)-dependent manner. Scatchard analysis of mJagged1 binding to BaF3 cells and to the soluble Notch2 protein demonstrated dissociation constants of 0.4 and 0.7 nM, respectively, and that the number of mJagged1-binding sites on BaF3 is 5,548 per cell. Furthermore, deletion mutant analyses showed that the DSL domain of mJagged1 is a minimal binding unit and is indispensable for binding to mNotch2. The epidermal growth factor-like repeats of mJagged1 modulate the affinity of the interaction, with the first and second repeats playing a major role. Finally, solid-phase binding assay showed that Jagged1 binds to Notch1 and Notch3 in addition to Notch2, suggesting that mJagged1 is a ligand for multiple Notch receptors.

Amino Acid Sequence↗
PubMed1999

Primed T cells are more resistant to Fas-mediated activation-induced cell death than naive T cells.

Memory T cells respond in several functionally different ways from naive T cells and thus function as efficient effector cells. In this study we showed that primed T cells were more resistant to Fas-mediated activation-induced cell death (AICD) than naive T cells using OVA-specific TCR transgenic DO10 mice and Fas-deficient DO10 lpr/lpr mice. We found that apoptosis was efficiently induced in activated naive T cells at 48 and 72 h after Ag restimulation (OVA peptide; 0.3 and 3 microM), whereas apoptosis was not significantly increased in activated primed T cells at 24-72 h after Ag restimulation. We further showed that the resistance to AICD in primed T cells was due to the decreased sensitivity to apoptosis induced by Fas-mediated signals, but TCR-mediated signaling equally activated both naive and primed T cells to induce Fas and Fas ligand expressions. Furthermore, we demonstrated that primed T cells expressed higher levels of Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein (FLIP), an inhibitor of Fas-mediated apoptosis, at 24-48 h after Ag restimulation than naive T cells. In addition, Bcl-2 expression was equally observed between activated naive and primed T cells after Ag restimulation. Thus, these results indicate that naive T cells are sensitive to Fas-mediated AICD and are easily deleted by Ag restimulation, while primed/memory T cells express higher levels of FLIP after Ag restimulation, are resistant to Fas-mediated AICD, and thus function as efficient effector cells for a longer period.

Animals↗
PubMed1999

Contact of hydroxyapatite spacers with split spinous processes in double-door laminoplasty for cervical myelopathy.

We developed a new type of spacer made of hydroxyapatite (the STSS spacer) for double-door laminoplasty, and evaluated the contact of 93 STSS spacers with the split spinous processes in 20 patients with double-door laminoplasty. Contact was assessed by measuring the extent of touch of the spacer to the spinous processes, classified into four categories based on computed tomography (CT) images: excellent, complete touch on both sides of the spacer to the spinous process; good, complete touch on one side and more than half touch on the other side; fair, more than half touch on both sides; poor, half or less touch on at least one side. Excellent contact was achieved in 65 spacers (69.9%); good, in 13 (14.0%); fair, in 11 (11. 8%); and poor, in 4 (4.3%). The percentages of excellent or good categories were 75.0% at the C3 level, 73.7% at the C4 level, 78.9% at the C5 level, 90.0% at the C6 level, and 100% at the C7 level. The contact rate of the STSS spacer with the spinous process was better than that achieved with other spacers, probably because the characteristic shape of the STSS spacer was compatible with the widened space between the bilateral spinous processes; i.e., it is trapezoidal on both the axial and the frontal sections. However, the appropriate size of the spacer must be selected in accordance with the size of the spinous process to obtain higher percentages of excellent or good contact.

Adult↗
PubMed1999

Underpants-pattern erythema: a previously unrecognized cutaneous manifestation of extramammary Paget's disease of the genitalia with advanced metastatic spread.

BACKGROUND: A previously unrecognized erythema was noted in 6 patients with extramammary Paget's disease (EMPD) of the genitalia with metastases. It was distinct from essential erythema of EMPD and has not been reported before. OBJECTIVE: Our purpose was to describe the clinical and histopathologic features of the erythema and clarify its pathogenesis and prognostic importance. METHODS: A review of the clinical records and histologic materials of 6 cases was made focusing on the clinical features of this unique erythema as well as the course and prognosis of the patients. RESULTS: The erythema first appeared in the inguinal region and extended centrifugally to an area normally covered by underpants. Histopathologic examination showed lymphatic infiltration by cancer cells of the skin. All of the patients with this "underpants-pattern erythema" died of the disease, and the mean survival period after its appearance was 13 months. CONCLUSION: Underpants-distribution erythema may be a sign of advanced stage EMPD.

Aged↗
PubMed1999

Differential diagnosis between glomerular and nonglomerular hematuria by automated urinary flow cytometer. Kitasato University Kidney Center criteria.

Objective, fast and easy methods have not been established in the examination of urine sediment to differentiate between glomerular and nonglomerular hematuria. In this study, we used a newly developed automated urinary flow cytometer that can clearly recognize red blood cells (RBC), white blood cells, epithelial cells, bacteria and crystals by their size and fluorescence intensity without sedimentation. 98 urine samples from 31 glomerular and 67 nonglomerular lesions were analyzed by the device, and the criteria to determine the origin of hematuria were established based on the results. Additional 108 cases were tested to evaluate the validity of these criteria. According to the analysis of histograms of urinary RBC size distribution, cases in whom >/=80% of all RBC have forward scatter (FSC) intensities </=126 and <80% of all RBC have FSC intensities >/=84 were regarded as representing the glomerular type. Cases in whom >/=80% of all RBC have intensities FCS >/=84 and <80% all RBC have FSC intensities </=126 were regarded as representing the nonglomerular type. Cases in whom <80% of all RBC have FSC intensities </=126 and <80% of all RBC have FCS intensities >/=84 were regarded as the mixed type. Cases in whom >/=80% of all RBC have FSC intensities </=126 and >/=80% of all RBC have FSC intensities >/=84 were regarded as the nonglomerular type. The sensitivity for glomerular RBC in the first 98 cases was 90.3% and the specificity 92.5%, and in the second 108 cases the values were 100 and 86.6%, respectively. The automated urinary flow cytometer is useful as a means for routine differential diagnosis of hematuria, and at least it is promising as the screening test for differentiation between glomerular and nonglomerular hematuria, because it can examine numerous samples within a short time and does not necessitate any special skill or knowledge.

Adolescent↗
PubMed1999

Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways.

Interleukin-18 (IL-18) has recently been identified as an IFN-gamma-inducing factor. Previous studies have shown that CD4(+) T cells, IL-5, and TNF-alpha mediate, but IFN-gamma and IL-12 (via IFN-gamma production) inhibit antigen-induced eosinophil recruitment into the airways of sensitized mice. Here, we showed that the administration of recombinant murine IL-18 enhanced antigen-induced eosinophil recruitment into the trachea and bronchoalveolar lavage fluids (BALF) of sensitized mice in a dose-dependent manner. The administration of IL-18 enhanced antigen-induced IFN-gamma and TNF-alpha production, but not IL-5 production, in the BALF and lungs of sensitized mice. Neutralizing antibody against TNF-alpha prevented antigen-induced eosinophil recruitment into the BALF of sensitized mice. Although IL-18 enhanced antigen-induced airway eosinophilia, IL-18 did not affect antigen-induced airway hyperresponsiveness in sensitized mice. These results indicate that IL-18, unlike IFN-gamma and IL-12, enhances antigen-induced eosinophil recruitment into the airways in part by increasing antigen-induced TNF-alpha production of sensitized animals. These findings suggest that IL-18 may contribute to the development and exacerbation of airway inflammation in asthma.

Analysis of Variance↗
PubMed1999

Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice.

TGF-beta plays an important role in lung fibrosis, which is a major cause of suffering and death seen in pulmonary disease. Smad7 has been recently identified as an antagonist of TGF-beta signaling. To investigate whether this novel molecule can be exploited for therapy of lung fibrosis, we determined the effect of exogenous Smad7, introduced by a recombinant human type 5 adenovirus vector, on bleomycin-induced lung fibrosis in mice. C57BL/6 mice with bleomycin-induced lungs received an intratracheal injection of a recombinant adenovirus carrying mice Smad7 cDNA. These mice demonstrated suppression of type I precollagen mRNA, reduced hydroxyproline content, and no morphological fibrotic responses in the lungs when compared with mice administered adenovirus carrying Smad6 cDNA. In addition, we found that expression of Smad7 transgene blocked Smad2 phosphorylation induced by bleomycin in mouse lungs. These data indicated that gene transfer of Smad7 (but not Smad6) prevented bleomycin-induced lung fibrosis, suggesting that Smad7 may have applicability in the treatment of pulmonary fibrosis.

Adenoviridae↗
PubMed1998

T-cell receptor variable gene analysis of renal allograft-infiltrating cells in biopsy specimens using a nonradioisotopic micromethod.

BACKGROUND: A sensitive micromethod for T-cell receptor (TCR) analysis is needed for clonality analysis of renal allograft-infiltrating T cells (RAITs) obtained by needle biopsy. METHODS: TCR cDNA was amplified by the anchored polymerase chain reaction and was hybridized with 28 different TCR beta variable (TCRBV) genes fixed on nylon membranes, and the percentage of each TCRBV gene was measured spectrophotometrically. RESULTS: The specificity and linearity of the hybridization technique and the constancy of the TCRBV percentages over a wide range of sample amounts were demonstrated by control experiments. Analysis of RAITs of biopsy specimens from four patients showed broad or skewed TCRBV usage, indicating the presence of polyclonal and oligoclonal RAIT populations, respectively. In one patient who received OKT3 immunosuppressive treatment, the TCRBV skewness was dramatically reduced after the treatment. CONCLUSION: We have established a powerful method for analyzing RAIT clonality, which is especially useful for monitoring RAIT dynamics after immunosuppression therapy.

Acute Disease↗
PubMed1998

A potential molecular approach to ex vivo hematopoietic expansion with recombinant epidermal growth factor receptor-expressing adenovirus vector.

Ex vivo expansion of hematopoietic stem cell (HSC) is an attractive technology for its potency of a variety of clinical applications. Such a technology has been achieved to some extent with combinations of various cytokines or continuous perfusion cultures. However, much more improvement is required especially for expansion of primitive hematopoietic progenitors. We propose here a novel molecular approach that might have the potential to compensate the current expansion. We designed an adenovirus vector to transiently express human epidermal growth factor receptor (EGFR), which is known to transduce only a mitogenic, but not a differentiation signal to mouse bone marrow cells on human purified CD34+ peripheral blood (PB) cells, and tried to expand these cells with EGF ex vivo. Because we found that exposure of CD34+ PB cells to cytokines induced surface expression of adenovirus-internalization receptor and rendered these cells permissive to adenovirus infection, we infected these cells with the adenovirus vector carrying EGFR gene in the presence of cytokines. Two-color flow cytometric analysis demonstrated that 60.3% +/- 22.4% of CD34+ cells expressed the adenovirus-mediated EGFR. Moreover, long-term culture-initiating cell assay showed that adenovirus vector could transduce more primitive progenitors. Subsequently, we tried to expand these cells in suspension culture with EGF for 5 days. Methylcellulose clonal assay showed that EGF induced 5.0- +/- 2.4-fold proliferation of the colony-forming unit pool during 5 days of expansion. The simple procedure of efficient adenovirus gene delivery to immature hematopoietic cells proved promising, and this technique was potentially applicable for a novel strategy aiming at ex vivo expansion of hematopoietic progenitors.

Adenoviridae↗
PubMed1998

Photosensitive dermatitis caused by pyridoxine hydrochloride.

Few photosensitive reactions caused by pyridoxine hydrochloride have been reported. There have been no reports of detailed photosensitivity studies on patients who have developed photosensitivity from pharmacologic doses of pyridoxine. Two patients with pyridoxine photosensitivity are described. Photopatch tests were positive for pyridoxine hydrochloride. The minimal erythematous dose (MED) for UVA decreased after the intravenous injection of pyridoxine hydrochloride in both patients. Normal controls gave negative results in photopatch tests for pyridoxine hydrochloride and phototest for vitamin B complex containing pyridoxine hydrochloride. On the basis of these results, we believe both patients had a photoallergic reaction to pyridoxine hydrochloride.

Dermatitis, Photoallergic↗
PubMed1998

Effect of probucol on serum lipoprotein and apoprotein profiles in renal transplant patients.

The therapeutic effect of probucol on hypercholesterolemia in cyclosporine A (CyA)-treated renal transplant patients was prospectively studied. Twelve posttransplantation patients aged 34.2+/-2.5 years with serum total cholesterol (t-CHL) of 250 mg/dL or greater, whose serum creatinine was 2.9 mg/dL or less, and who had no diabetes mellitus or hypoproteinemia, were treated with probucol, 250 mg twice daily for 3 months. Seventeen age-matched (36.8+/-1.6 years) normal volunteers served as control. Blood was drawn after at least a 12-hour fast to measure lipids in serum and lipoprotein fractions, apoproteins (apo), lipoprotein fractions, lethicin cholesterol acyl transferase (LCAT), free fatty acids (FFA), and CHL-ester. Serum t-CHL, triglycerides (TG), and phospholipids (PL) in posttransplantation patients before treatment were significantly higher compared with normal control subjects. Very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) fractions in these patients were significantly expanded. The pretreatment levels of serum apo AII, B, CII, and CIII were significantly increased compared with those of normal controls. After treatment with probucol, serum t-CHL, LDL-CHL, high-density lipoprotein (HDL)-CHL, PL, LDL-PL, and apo AI were significantly decreased, and CHL-ester significantly increased compared with the pretreatment levels. These data suggest that although probucol causes a decrease in HDL-CHL, it may act anti-atherogenically by modulating HDL metabolism and stimulating reverse transfer of CHL from peripheral tissue.

Adult↗
PubMed1998

Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is a rare disorder characterized by congenital anomalies of the upper limbs and heart. Cardiac arrhythmias are common in patients with HOS. We successfully managed a 24-yr-old woman with HOS who underwent laparoscopic ovarian cystectomy. Potential problems in the anaesthetic management of patients with HOS are discussed.

Adult↗
PubMed1998

High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the mouse airways.

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and IL-5. To determine whether the induction of oral tolerance down-regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of oral administration of a protein antigen on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on antigen-induced CD4+ T cell infiltration and IL-5 production in the airways, and on the in vitro production of IL-2, IL-4, IL-5 and IFN-gamma in spleen cells of the mice. Oral administration of a protein antigen in high doses inhibited antigen-induced eosinophil infiltration in the trachea and IgE antibody production in mice in an antigen-specific manner. The oral administration of antigen also suppressed both CD4+ T cell recruitment into the trachea and IL-5 levels in the bronchoalveolar lavage fluids of the mice after antigen inhalation. In vitro antigen-induced production of IL-2, IFN-gamma, IL-4 and IL-5 was decreased in spleen cells of antigen-fed mice, indicating the induction of both Th1 and Th2 cell tolerance in vivo. On the other hand, pretreatment with anti-transforming growth factor-beta antibody at the time of immunization with antigen had no significant effect on the inhibition of antigen-induced eosinophil recruitment and IgE antibody production in antigen-fed mice. Finally, antigen-specific CD4+ T cells were not deleted in TCR transgenic mice after antigen feeding by FACS analysis. Taken together, these results indicate that high-dose oral tolerance induces not only Th1 but also Th2 cell tolerance in vivo and thereby inhibits antigen-induced eosinophil recruitment into the tissue.

Administration, Oral↗